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Pharmacotherapy of helminth infection
No full textBACKGROUND: In the first decade of the 21st century, worm infections are still very common, especially--but not exclusively--in the developing world. OBJECTIVE: To review the current pharmacotherapy of the major trematode, cestode and nematode infections of humans. METHODS: A systematic search of the Cochrane Databank of Controlled Trials and PubMed with MeSH terms (anthelmint(*) or treatment or therapy) and (cestoda or trematoda or nematoda or specific helminth species or specific medication). Further references were obtained from article biobliographies. RESULTS: Three hundred and twenty-six publications were selected for further review. CONCLUSION: Albendazole, praziquantel and ivermectin are the most important anthelmintics available, easy to use and active against most helminths. Diethylcarbamazine is used in loasis and lymphatic filariasis. Doxycycline can eliminate endosymbiotic bacteria of certain filariae, but its place in therapy needs to be further defined. In the treatment of cystic hydatid disease, a better, non-caustic protoscolicidal drug would diminish the complication rate of current puncture-aspiration-injection-reaspiration treatment. The reliance on so few drugs creates a dangerous situation for development of resistance. Triclabendazole is a welcome addition for fascioliasis. Tribendimidine, artemisinine derivatives and nitazoxanide are promising products, but their therapeutic place needs to be further defined
Pulmonary tuberculosis case detection through fortuitous cough screening during home visits
No full textThe definitive version is available at www3.interscience.wiley.co
Disco funerals: a risk situation for HIV infection among youth in Kisumu, Kenya
No full textOBJECTIVE: We investigated the so-called 'disco funeral' phenomenon in Kisumu, Kenya, whereby community members including adolescents congregate at the home of the deceased for several days, accompanied by music and dancing. We explored whether disco funerals are a risk situation for HIV/sexually transmitted infection infection among youth. DESIGN:: Cross-sectional qualitative study. METHODS: We conducted 44 in-depth interviews with male and female adolescents aged 15-20 years in Kisumu municipality in Nyanza Province, Kenya. We also made observations during six disco funerals. RESULTS: Disco funerals were an important place for young people to hang out; they increased the opportunities to meet and engage in (risky) sexual activities. Many adolescents reported having casual sex on these occasions, sometimes with multiple partners, and mostly without condoms. Some girls were forced into sex, and there were several accounts of gang rape. Sex in exchange for money was reported frequently. Drugs and alcohol seemed to facilitate unprotected, multiple-partner, coerced, and transactional sex. CONCLUSION: In Kisumu, a town with a generalized HIV/AIDS epidemic, the high AIDS mortality leads to frequent disco funerals. Because many adolescents are having unprotected, transactional, or coerced sex at these occasions, disco funerals might contribute to the high HIV prevalence among youth, especially among adolescent girls. HIV interventions urgently need to include outreach actions to youth who hang out at disco funerals and link up with parents and funeral organizers to reduce risk situations
PCR and direct agglutination as Leishmania infection markers among healthy Nepalese subjects living in areas endemic for kala-azar
No full textOBJECTIVE: To compare a PCR assay and direct agglutination test (DAT) for the detection of potential markers of Leishmania infection in 231 healthy subjects living in a kala-azar endemic focus of Nepal. METHODS: The sample was composed of 184 (80%) persons without any known history of KA and not living in the same house as known kala-azar cases (HNK), 24 (10%) Healthy Household Contacts (HHC) and 23 (10%) past kala-azar cases which had been successfully treated (HPK). RESULTS: PCR and DAT positivity scores were, respectively: HNK, 17.6% and 5.6%; HHC, 12.5% and 20.8%; HPK, 26.1% and 95.7%. The ratio PCR-positives/DAT-positives was significantly higher in HNK (ratio = 3.1) than in HHC (ratio = 0.6, P = 0.036) and in HPK (ratio = 0.2, P = 0.012). The ratio PCR-positives/DAT-positives did not significantly differ between HHC (ratio = 0.6) and HPK (ratio = 0.2, P = 0.473). The positive agreement index between PCR and DAT in HNK was 5%; in HHC, 0%; in HPK, 43%. CONCLUSIONS: Our study highlights the specific character of PCR and DAT for the exploration of Leishmania asymptomatic infections. PCR is probably more informative for very recent infections among HNK, while DAT provides more information among HHC and HPK, a feature likely related to the power of serology to track less recent infections
Development and evaluation of a clinical algorithm to monitor patients on antiretrovirals in resource-limited settings using adherence, clinical and CD4 cell count criteria
No full textBACKGROUND: Routine viral load monitoring of patients on antiretroviral therapy (ART) is not affordable in most resource-limited settings. METHODS: A cross-sectional study of 496 Ugandans established on ART was performed at the Infectious Diseases Institute, Kampala, Uganda. Adherence, clinical and laboratory parameters were assessed for their relationship with viral failure by multivariate logistic regression. A clinical algorithm using targeted viral load testing was constructed to identify patients for second-line ART. This algorithm was compared with the World Health Organization (WHO) guidelines, which use clinical and immunological criteria to identify failure in the absence of viral load testing. RESULTS: Forty-nine (10%) had a viral load of >400 copies/mL and 39 (8%) had a viral load of >1000 copies/mL. An algorithm combining adherence failure (interruption >2 days) and CD4 failure (30% fall from peak) had a sensitivity of 67% for a viral load of >1000 copies/mL, a specificity of 82%, and identified 22% of patients for viral load testing. Sensitivity of the WHO-based algorithm was 31%, specificity was 87%, and would result in 14% of those with viral suppression (<400 copies/mL) being switched inappropriately to second-line ART. CONCLUSION: Algorithms using adherence, clinical and CD4 criteria may better allocate viral load testing, reduce the number of patients continued on failing ART, and limit the development of resistance
Absence of knockdown resistance suggests metabolic resistance in the main malaria vectors of the Mekong region
No full textBACKGROUND: As insecticide resistance may jeopardize the successful malaria control programmes in the Mekong region, a large investigation was previously conducted in the Mekong countries to assess the susceptibility of the main malaria vectors against DDT and pyrethroid insecticides. It showed that the main vector, Anopheles epiroticus, was highly pyrethroid-resistant in the Mekong delta, whereas Anopheles minimus sensu lato was pyrethroid-resistant in northern Vietnam. Anopheles dirus sensu stricto showed possible resistance to type II pyrethroids in central Vietnam. Anopheles subpictus was DDT- and pyrethroid-resistant in the Mekong Delta. The present study intends to explore the resistance mechanisms involved. METHODS: By use of molecular assays and biochemical assays the presence of the two major insecticide resistance mechanisms, knockdown and metabolic resistance, were assessed in the main malaria vectors of the Mekong region. RESULTS: Two FRET/MCA assays and one PCR-RFLP were developed to screen a large number of Anopheles populations from the Mekong region for the presence of knockdown resistance (kdr), but no kdr mutation was observed in any of the study species. Biochemical assays suggest an esterase mediated pyrethroid detoxification in An. epiroticus and An. subpictus of the Mekong delta. The DDT resistance in An. subpictus might be conferred to a high GST activity. The pyrethroid resistance in An. minimus s.l. is possibly associated with increased detoxification by esterases and P450 monooxygenases. CONCLUSION: As different metabolic enzyme systems might be responsible for the pyrethroid and DDT resistance in the main vectors, each species may have a different response to alternative insecticides, which might complicate the malaria vector control in the Mekong region
Global health actors claim to support health system strengthening; is this reality or rhetoric?
No full textAn institutional economic analysis of public health care organisations in low-income countries
No full textLow-income countries still face a number of major health challenges. Public health services
respond to them with great difficulty. This low performance is traditionally attributed to a lack of
resources. Our hypothesis is that the observed low performance stems also from the very way
that the public health systems are institutionally established. Our belief is that the institutional
dimension has not been correctly appreciated so far in theories and policies of health service
organisation in low-income countries. Our general strategy is to tap recent developments in
organisational economic theory to get more insights in the related scientific questions and the
connected health policy issues. Our investigation is organised in two parts.
Part 1 aims mainly at validating the utilisation of economics (and its institutional branches in
particular) to analyse the organisation of public health system. This validation is done in
successive steps. In our chapter 1, we introduce public health systems in rural areas in lowincome
countries. This largely descriptive and historical chapter is helpful to provide the
situation of reference discussed throughout the thesis.
With the next chapters, we shift to economic theory. Our chapter 2 provides a review of recent
development in the economics of institutions; it sketches the overall theoretical background and
allows us to situate our own research program in this panorama. The next four chapters are
dedicated to concepts that are helpful for the economic study of public health systems, concepts
that we draw from this literature. Our chapters 3 and 4 introduce respectively the concepts of
institutions and organisations. In our chapters 5 and 6, we highlight how institutions structure
property rights and how property rights set incentives to economic agents. This tedious
application of organisational economics to our case of study allow us to highlight a few pending
conceptual questions in institutional economic theories.
In our chapter 7, we put these different concepts together and propose an institutional economic
framework to study public health care organisations. Among other things, we show that this
framework can help to structure the study of the performance of the public health systems. In
our chapter 8, we come back to the rural health systems introduced in our chapter 1. Thanks to
our institutional economic framework, we put forward a new explanation for the low
performance of public health systems.
Part 2 of the thesis explores the reform alternatives. Our chapter 9 is dedicated to the empirical
scrutiny of two recent reforms: the Performance Initiative in Rwanda and the Health Equity
Fund in Cambodia. The chapter consists in a collection of four papers published in peerreviewed
public health journals. Each paper is introduced and linked to the first part of the
thesis. Our chapter 10 is the prescriptive one. We propose ways forward for reforming public
health systems in low-income countries. Whereas our ten ‘propositions’ are to some extent
speculative, they are clear enough to be falsifiable in the future. This allows us to identify some
possible tracks for the expansion of our research program.
Our thesis ends with a conclusion highlighting our contribution to the scientific and policy
debate
The diarylquinoline TMC207 for multidrug-resistant tuberculosis
No full textBACKGROUND: The diarylquinoline TMC207 offers a new mechanism of antituberculosis action by inhibiting mycobacterial ATP synthase. TMC207 potently inhibits drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro and shows bactericidal activity in patients who have drug-susceptible pulmonary tuberculosis. METHODS: In the first stage of a two-stage, phase 2, randomized, controlled trial, we randomly assigned 47 patients who had newly diagnosed multidrug-resistant pulmonary tuberculosis to receive either TMC207 (400 mg daily for 2 weeks, followed by 200 mg three times a week for 6 weeks) (23 patients) or placebo (24 patients) in combination with a standard five-drug, second-line antituberculosis regimen. The primary efficacy end point was the conversion of sputum cultures, in liquid broth, from positive to negative. RESULTS: The addition of TMC207 to standard therapy for multidrug-resistant tuberculosis reduced the time to conversion to a negative sputum culture, as compared with placebo (hazard ratio, 11.8; 95% confidence interval, 2.3 to 61.3; P=0.003 by Cox regression analysis) and increased the proportion of patients with conversion of sputum culture (48% vs. 9%). The mean log(10) count of colony-forming units in the sputum declined more rapidly in the TMC207 group than in the placebo group. No significant differences in average plasma TMC207 concentrations were noted between patients with and those without culture conversion. Most adverse events were mild to moderate, and only nausea occurred significantly more frequently among patients in the TMC207 group than among patients in the placebo group (26% vs. 4%, P=0.04). CONCLUSIONS: The clinical activity of TMC207 validates ATP synthase as a viable target for the treatment of tuberculosis. (ClinicalTrials.gov number, NCT00449644.